Deck 22: Stem Cells and Tissue Renewal

Question 1

Each gut stem cell …

A) is pluripotent.
B) divides approximately once a week.
C) gives rise to all four major epithelial cell types in the right proportions.
D) expresses Lgr5, just like the epithelial cells that derive from it.
E) All of the above.

Answer 1

C
Explanation: The Lgr5-positive gut stem cells are multipotent and divide approximately once a day. D is incorrect because the epithelial cells that are produced from these stem cells no longer express Lgr5.

Question 2

Stem cells …

A) always divide asymmetrically to give rise to two different daughter cells.
B) are terminally differentiated.
C) can divide for the entire lifetime of the organism.
D) divide at a relatively fast rate.
E) All of the above.

Answer 2

C
Explanation: Stem cells are not terminally differentiated, and can self-renew by unlimited divisions (at least for the lifetime of the animal). When they divide, which they usually do at a slow pace, each daughter cell has a choice of whether or not to remain as a stem cell.

Question 3

If some cells in an adult mammal are lost, they are lost forever and cannot be replaced. Which of the following cell types have such a limitation? Your answer would be a string composed of a subset of the letters A to E in alphabetical order, e.g. AE.
(A) Photoreceptive epithelium of the retina
(B) ? Cells of pancreatic islets
(C) Hepatocytes of the liver
(D) Auditory epithelium of the inner ear
(E) Olfactory epithelium of the nose

Answer 3

AD

Question 4

The differentiation of bone marrow stromal cells into bone or fat cells depends on chemical and mechanical signals. In each of the following conditions, indicate whether you would expect the stromal cells to differentiate into bone (B) or fat (F) cells. Your answer would be a three-letter string composed of letters B and F only, e.g. FBB.
( ) The cells are embedded in a stiff hydrogel.
( ) The cells are embedded in a soft hydrogel.
( ) The cells are treated with a Rho inhibitor. The monomeric GTPase Rho is required for the assembly of actin stress fibers and actin-myosin bundles.

Question 5

Radial glial cells are stem cell-like neural progenitors in the adult mammalian brain and can give rise to a number of differentiated neural cell types. Knowing that quiescent radial glial cells uniquely express the cytoskeletal protein nestin, a researcher performed clonal analysis in mice to study the characteristics of radial glial cells and their descendants. She created transgenic mice expressing Cre recombinase under the control of the nestin regulatory sequences. She also created transgenic mice that carry the gene encoding the green fluorescent protein (GFP) under the control of a ubiquitous promoter. The GFP-encoding gene, however, is inactive unless recombination by Cre removes a blocking sequence between the promoter and the gene. After mating these mice, she obtains adult mice carrying both transgenes and injects them with a low dose of tamoxifen to activate Cre sporadically. After a month, she uses microscopy to study the cells of the brain hippocampus. She discovers that most neural cell types in the tissue, including neurons, develop from the radial glial cells. Oligodendrocytes, however, appear to derive from another stem-cell population. Based on her conclusions, which cells do you think expressed GFP after a month: neurons (N) or oligodendrocytes (O)? If a single isolated GFP-expressing cell is observed in the tissue, would you expect it to be a differentiated cell (D) or a radial glial cell (R)? If a larger clone is observed to be entirely made of radial glial cells, would a symmetric (S) or asymmetric (A) model be favored for the strategy of cell divisions in these cells? Write down your answer as a three-letter string, e.g. NDA.

Question 6

Indicate true (T) and false (F) statements below regarding bone and bone remodeling. Your answer would be a four-letter string composed of letters T and F only, e.g. FFFF.
( ) Cells that demolish old bone matrix are related to macrophages of the immune system.
( ) Bone is over 99% nonliving material.
( ) A blood capillary can form as bone is excavated during remodeling.
( ) Tunnels made by osteoclasts are immediately and fully refilled by osteoblasts.

Question 7

Indicate whether each of the following descriptions better matches bone (B) or cartilage (C). Your answer would be a four-letter string composed of letters B and C only, e.g. CCCC.
( ) Its extracellular matrix is mainly composed of type I collagen and calcium crystals.
( ) Its extracellular matrix is made by osteoblasts.
( ) It grows by expansion (as opposed to surface apposition).
( ) Its cells are connected via canaliculi and form gap junctions.

Question 8

In some adenomas of the colon, intestinal crypt cells appear to have proliferated abnormally to form small tumors known as polyps. Studies on the familial type of such a disease led to the identification of a major signaling pathway (which was aberrant in the polyp cells) as being involved in the maintenance of the gut stem-cell compartment. What signaling pathway is this? Is it upregulated or downregulated in colon cancers?

A) MAPK pathway; up-regulated
B) MAPK pathway; down-regulated
C) Wnt pathway; up-regulated
D) Wnt pathway; down-regulated
E) Hedgehog pathway; down-regulated

Question 9

Which of the following cell types in our body are typically renewed independently of stem cells? Your answer would be a string composed of a subset of the letters A to E in alphabetical order, e.g. BDE.
(A) Red blood cells
(B) ? Cells of pancreatic islets
(C) Hepatocytes of the liver
(D) Epithelial cells of the epidermis
(E) Neutrophils of the blood

Question 10

How is the organization of epithelial cells in epidermis different from that in the lining of the intestine?

A) The epidermis is stratified and squamous (i.e. forms squames).
B) The stem-cell niche in epidermis is provided by the basal lamina and the underlying connective tissue.
C) The transit amplifying cells in the epidermis move mostly perpendicular to the plane of the epithelium.
D) The cells of the epidermis die long before they are shed.
E) All of the above.

Question 11

Indicate whether each of the following descriptions better applies to an asymmetric (A) or a symmetric (S) stem-cell division strategy. Your answer would be a four-letter string composed of letters A and S only, e.g. AAAA.
( ) It predicts the number of stem cells in a population to remain strictly constant after several rounds of cell division.
( ) Cytoplasmic factors that control stemness are localized to one side of the cell before cytokinesis.
( ) It is a more flexible strategy and can better accommodate the effect of environmental factors.
( ) It is more consistent with observations in gut stem cells and other stem cells.

Question 12

Which of the following statements is true regarding skeletal muscle development and regeneration in humans?

A) Muscle is among those tissues that cannot be renewed once damaged.
B) Myoblasts are multipotent stem cells.
C) Muscle regeneration occurs as a result of stimulation of quiescent stem cells in the periphery of muscle fibers.
D) A muscle that has been repaired once cannot be repaired again.

Question 13

Indicate whether each of the following descriptions better applies to cardiac (C), skeletal (K), myoepithelial (M), or smooth (O) muscle cells. Your answer would be a four-letter string composed of letters C, K, M, and O only, e.g. MMKC.
( ) They are derived from the ectoderm layer, similar to epithelial cells.
( ) They form the lining of cavities such as the urinary bladder.
( ) They are responsible for most voluntary muscle movements.
( ) They form multinucleated and exceptionally long muscle fibers.

Question 14

The schematic drawing below shows the cross section of a crypt in the gut epithelium of a mammal. Indicate whether each of the following descriptions better applies to the areas labeled A, B, or C. Your answer would be a four-letter string composed of letters A to C only, e.g. CCBB.

( ) The stem cells reside in this area.
( ) This area contains the most rapidly dividing cells.
( ) Cells in this area would show the least radioactivity following a pulse of tritiated thymidine.
( ) This area contains cells of the innate immune system.

Question 15

Lymphatic capillaries …

A) are lined with endothelial cells.
B) have leakier walls compared to blood capillaries.
C) can provide a path for cancer metastasis.
D) All of the above.

Question 16

In addition to fibroblasts themselves, the fibroblast family of connective-tissue cells includes all of the following EXCEPT …

A) Smooth muscle cells
B) Chondrocytes
C) Osteoblasts
D) Adipocytes
E) Macrophages

Question 17

In each of the following examples of contact signaling between adjacent cells in the mammalian gut epithelia, indicate whether the signaling is mainly mediated by Delta (D) or Ephrin (E) signals. Your answer would be a three-letter string composed of letters D and E only, e.g. EDE.
( ) Separation of crypt cell types from villus cell types
( ) Regulation of stem-cell differentiation by Paneth cells
( ) Differentiation of transit amplifying cells into either secretory cells or absorptive cells

Question 18

Which of the following cells in a healthy adult human show the highest turnover?

A) Neurons of the hippocampus
B) Epithelial cells of the urinary tract
C) Hepatocytes of the liver
D) Epithelial cells of the small intestine
E) Neutrophils of the blood

Question 19

Considering the role of Notch and Wnt signaling pathways in epithelial cell differentiation in the mammalian intestine, indicate whether each of the following changes in "minigut" organoids in culture is expected to lead to a higher (H) or lower (L) number of stem cells. Your answer would be a two-letter string composed of letters H and L only, e.g. HH.
( ) RNA interference knockdown of Hes1, an essential downstream effector of the Notch signaling pathway
( ) Deletion of the gene encoding Apc, a gene that is mutated in many colorectal cancers

Question 20

Indicate true (T) and false (F) statements below regarding the pattern of cell proliferation in the epithelium that forms the lining of the small intestine. Your answer would be a four-letter string composed of letters T and F only, e.g. TTTT.
( ) New epithelial cells are constantly born throughout the epithelial sheet, mostly at the villi.
( ) Every type of intestinal epithelial cell is eventually discarded into the gut lumen where they die.
( ) There is a net movement of cells from the bottom of the crypts up toward the tip of the villi.
( ) The majority of intestinal epithelial cells have packed microvilli on their apical surfaces.

Question 21

All blood cells in our body …

A) have exceptionally short life-spans-at most a month or so.
B) are produced only before adulthood.
C) are ultimately generated from multipotent hematopoietic stem cells.
D) are made from progenitors that themselves circulate in the blood.
E) All of the above.

Question 22

Sort the following cell types from high to low abundance in the blood (number of cells per unit volume) in a healthy individual. Your answer would be a four-letter string composed of letters A to D only, e.g. BADC.
(A) Erythrocytes
(B) Neutrophils
(C) Basophils
(D) T lymphocytes

Question 23

Stem cells can be obtained from self-renewing regions of an adult vertebrate brain, cultured in suspension or in monolayer, and later grafted back into a live animal. When implanted, stem cells isolated from mouse hippocampus …

A) can only give rise to hippocampus neurons, even in a different location in the brain.
B) can give rise to neurons in another part of the brain, e.g. in the olfactory bulb.
C) are unable to proliferate unless implanted in the hippocampus, where they contribute to its neurons.
D) can give rise to any cell (e.g. muscle cells) when implanted into muscle tissue.

Question 24

Fill in the blank in the following paragraph. Do not use abbreviations.
"Growth and branching of blood vessels by the process of … creates a highly branched network of blood vessels and capillaries to ensure that almost every cell within our body has access to nutrients and oxygen from a nearby capillary. This process is distinct from de novo vasculogenesis during embryonic development."

Question 25

A physician had prescribed a differential white blood cell count to help diagnose a sick child with sustained fever and weight loss. The results show a significant increase in the number of eosinophils beyond the normal range for healthy individuals. This is most likely due to …

A) bacterial infection.
B) parasitic infection.
C) viral infection.
D) kidney failure.
E) internal bleeding.

Question 26

Blood platelets in an adult human …

A) are made in lymphoid organs.
B) are NOT derived from hematopoietic stem cells.
C) lack nuclei.
D) All of the above.

Question 27

Which mammalian blood cell type undergoes the developmental event shown schematically in the following drawing as part of its maturation?

A) Monocyte
B) Megakaryocyte
C) Erythrocyte
D) Lymphocyte
E) Granulocyte

Question 28

An increasing number of lymphomas are being treated with "stem-cell transplantation" therapy that is composed of the following overall steps. Sort these steps into the correct order. Your answer would be a three-letter string composed of letters A to C only, e.g. BAC.
(A) Injection of cells into the blood
(B) Harvesting and isolating selected cells from the patient's bone marrow
(C) Heavy x-ray irradiation of the patient

Question 29

Indicate true (T) and false (F) statements below regarding erythropoiesis. Your answer would be a four-letter string composed of letters T and F only, e.g. TTTF.
( ) Oxygen stimulates the secretion of erythropoietin.
( ) Each human erythrocyte lives for a few days on average.
( ) All erythrocytes express "DON'T EAT ME" signals on their surface to prevent phagocytosis.
( ) It only takes 1 to 2 days for erythrocyte numbers to rise following stimulation with erythropoietin.

Question 30

Indicate true (T) and false (F) statements below regarding blood leukocytes. Your answer would be a four-letter string composed of letters T and F only, e.g. TTTT.
( ) Most white blood cells use blood merely as a transportation medium, and function in other tissues.
( ) Some granulocytes are professional phagocytes.
( ) Monocytes typically give rise to macrophages and polymorphonuclear leukocytes.
( ) Natural killer cells have a lymphoid origin.

Question 31

Sort the following events to reflect the order in which they occur for formation of new blood capillaries in conditions of insufficient oxygen supply. Your answer would be a four-letter string composed of letters A to D only, e.g. DACB.
(A) New tip cells are formed on the sides of nearby capillaries.
(B) Stalk cells divide and hollow out to form tubes.
(C) VEGF is secreted by the cell.
(D) The level of intracellular HIF1? increases.

Question 32

Using Cre recombination, the gene encoding stem cell factor (SCF) can be deleted in specific cell types in adult mice. Deletion of this gene in which of the following cells would you expect to lead to the most significant depletion of hematopoietic stem cells in the bone marrow?

A) Osteoblasts
B) Osteoclasts
C) Stromal cells
D) Hematopoietic stem cells
E) Common myeloid precursor cells

Question 33

Cells of the inner cell mass in an early mammalian embryo can be isolated and grown in culture. Which of the following is NOT true regarding these cells?

A) They are totipotent.
B) They can be introduced into another developing embryo where their progeny become incorporated into the resulting adult animal, even into its germ line.
C) They are stem cells.
D) They can be manipulated in culture to give rise to almost any type of differentiated cell.

Question 34

Indicate true (T) and false (F) statements below regarding differentiation of blood cells. Your answer would be a four-letter string composed of letters T and F only, e.g. TTTT.
( ) Most blood cells are derived from the pluripotent stem cells by a few cell divisions.
( ) Commitment to a specific differentiation path is a stepwise process.
( ) Upon contacting connective-tissue cells of the bone marrow, hematopoietic stem cells lose their stem-cell character and differentiate.
( ) Committed hematopoietic progenitor cells typically divide rapidly.

Question 35

A researcher is studying limb regeneration in the newt Notophthalmus viridescens. She transplants skeletal muscle cells from a transgenic newt that expresses green fluorescent protein (GFP) in all of its cells into the limb of a wild-type recipient newt. She then amputates the recipient limb right at the site of the graft, such that the stump contains GFP-expressing cells. She repeats this experiment several times. Where would you expect to detect GFP in the resulting regenerated limbs?

A) Only in muscle cells.
B) Only in skin cells.
C) Only in nerve cells.
D) Only in muscle and skin cells.
E) In all of the cells.

Question 36

Although quite inefficient, cloning by nuclear transplantation can be successful, as exemplified by cloning of the famous Dolly. Such a success implies that …

A) nuclei can be reprogrammed by cytoplasmic factors in a foreign cytoplasm.
B) epigenetic changes in somatic cells are not functionally irreversible.
C) even a differentiated nucleus contains a complete genome, capable of supporting the development of an entire organism.
D) All of the above.

Question 37

Indicate true (T) and false (F) statements below regarding the regenerative capacity of the planarian Schmidtea mediterranea. Your answer would be a four-letter string composed of letters T and F only, e.g. TTTF.
( ) When the animal is starved, some of its cells are cannibalized by other cells.
( ) The differentiated cells in the animal's body are continually replaced.
( ) Even a single healthy cell can rescue a lethally irradiated animal from death.
( ) Only neoblasts are capable of rescuing a lethally irradiated animal from death.

Question 38

If a hematopoietic cell is deprived of colony-stimulating factors, it typically …

A) dies by apoptosis.
B) differentiates randomly into several cell types.
C) differentiates randomly to one cell type.
D) enters a quiescent state.
E) divides without differentiating.

Question 39

BrdU (bromodeoxyuridine) is a thymidine analog that can be naturally incorporated into DNA (in place of thymidine) and detected by specific anti-BrdU antibodies. In an experiment to study the regeneration capabilities of Schmidtea mediterranea, you first fed the worms with BrdU-containing food for 30 minutes. After two hours, you fixed and incubated the worms with a fluorescently labeled anti-BrdU antibody, and observed its tissues with a fluorescence microscope. The result was that some nuclei are labeled with fluorescence while others are unlabeled. Would you expect to observe neoblasts mostly among cells that have (Y) or have not (N) been labeled with fluorescence? Are the neoblasts expected to be scattered throughout the body (S) or localized to a certain region (L)? If you fixed the worms after a week, instead of two hours, would you expect the number of nuclei with detectable fluorescence to increase (I), remain unchanged (U), or decrease (D) compared to these results? Write down your answer as a three-letter string, e.g. YSD.

Question 40

The GM progenitor cell gives rise to two main classes of white blood cells in the presence of appropriate colony-stimulating factors. Both of these cell types …

A) have relatively long half-lives, being capable of living for months if not years.
B) circulate in the bloodstream for most of their life-span.
C) are phagocytes.
D) are unaffected by colony-stimulating factors once terminally differentiated.
E) All of the above.

Question 41

Only cells that express a puromycin-resistance (PR) gene can grow in the presence of the drug puromycin. Ganciclovir is a nontoxic drug that is converted to a lethal toxin in a cell that expresses thymidine kinase (TK). Thy-1 is a fibroblast-specific marker protein. Which of the following selection strategies is the most reasonable one to use in experiments that attempt to generate induced pluripotent stem cells (iPS cells) from fibroblasts?

A) Engineering fibroblasts to express PR under the control of the Nanog promoter, and selecting iPS cells in puromycin-containing media
B) Engineering fibroblasts to express PR under the control of the Thy-1 promoter, and selecting iPS cells in puromycin-containing media
C) Engineering fibroblasts to express TK under the control of the Nanog promoter, and selecting iPS cells in ganciclovir-containing media
D) Engineering fibroblasts to express TK under the control of the Thy-1 promoter, and selecting iPS cells in ganciclovir-containing media
E) Engineering fibroblasts to express TK under the control of the Thy-1 promoter, and selecting iPS cells in puromycin-containing media

Question 42

Which group of factors is thought to impede iPS cell generation from a differentiated cell, inasmuch as the reprogramming efficiency is increased when the activity of the factors is decreased?

A) Histone acetyl transferases
B) Histone deacetylases
C) Chromatin remodelers
D) DNA demethylases
E) All of the above

Question 43

Sort the following events to reflect the order in which they typically take place during the reprogramming of fibroblasts to induced pluripotent stem cells. Your answer would be a four-letter string composed of letters A to D only, e.g. ADBC.
(A) Sustained endogenous expression of Oct4
(B) Gain of embryonic marker protein
(C) Loss of fibroblast-specific marker protein
(D) OSKM overexpression

Question 44

Which of the following tasks is possible with current stem-cell and reprogramming technology?

A) Guiding ES cells to generate any desired adult cell type.
B) Generating functional whole organs from iPS cells for transplantation.
C) Forcing transdifferentiation of any terminally differentiated cell into another cell.
D) In vitro screening for drug discovery using patient-specific iPS-derived cells as disease models.
E) All of the above.

Question 45

Which of the following transcription regulators constitute the master set of transcription regulatory proteins whose expression is most required for generating induced pluripotent stem cells and for maintaining pluripotency? Choose three proteins. Your answer would be a three-letter string composed of letters A to F in alphabetical order, e.g. CEF.
(A) Myc
(B) Klf4
(C) MyoD
(D) Nanog
(E) Oct4
(F) Sox2