Exam 22: Stem Cells and Tissue Renewal

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.

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

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.

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?

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 …

Lymphatic capillaries …

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

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?

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

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?

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.

Stem cells …

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?

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

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

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."

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

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

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

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.